J Chem Inf Model. 2020 Sep 28;60(9):4144-4152. doi: 10.1021/acs.jcim.0c00113. Epub 2020 May 1.
Two orthogonal approaches for hit identification in drug discovery are large-scale and screening. In recent years, due to the emergence of new targets and a rapid increase in the size of the readily synthesizable chemical space, there is a growing emphasis on the integration of the two techniques to improve the hit finding efficiency. Here, we highlight three examples of drug discovery projects at Merck & Co., Inc., Kenilworth, NJ, USA in which different virtual screening (VS) techniques, each specifically tailored to leverage knowledge available for the target, were utilized to augment the selection of high-quality chemical matter for assays and to enhance the diversity and tractability of hits. Central to success is a fully integrated workflow combining and experimental expertise at every stage of the hit identification process. We advocate that workflows encompassing VS as part of an integrated hit finding plan should be widely adopted to accelerate hit identification and foster cross-functional collaborations in modern drug discovery.
两种用于药物发现的命中鉴定的正交方法是大规模筛选和筛选。近年来，由于新靶标的出现和可合成化学空间的迅速扩大，越来越重视将这两种技术集成起来，以提高命中发现效率。在这里，我们强调了美国新泽西州肯尼沃斯的默克公司（Merck & Co.， Inc.）的三个药物发现项目的例子，其中使用了不同的虚拟筛选（VS）技术，每个技术都专门针对利用目标的可用知识进行了调整，以增加高质量化学物质的选择用于测定，并提高命中的多样性和可操作性。成功的关键是在命中鉴定过程的每个阶段都结合了和实验专业知识的完全集成的工作流程。我们主张将 VS 作为综合命中发现计划的一部分的工作流程应该被广泛采用，以加速命中发现，并促进现代药物发现中的跨职能合作。
